MiR-493-5p inhibits Th9 cell differentiation in Allergic Asthma by
targeting FOXO1
Abstract
Background:There is an increasing attention on miRNAs because of their
functional effect on polarization of CD4+ T cells. This study explores
the mechanism of miR-493-5p regulating Th9 cell differentiation in
allergic asthma. Methods: The allergic airway inflammation is induced by
Ovalbumin(OVA)in mice. CD4+ T cells from normal mice are cultured under
Th9 cell conditions. IL-9 levels in mice and CD4+T cells are analyzed by
RT-qPCR, ELISA, flow cytometry and western blot. The miR-493-5p levels
in mice and cells are detected by RT-qPCR. The interaction between FOXO1
and miR-493-5p is predicted by TargetScan and confirmed by dual
luciferase assay. The pathological state is evaluated by H&E staining
and Lung resistance is measured in the allergic mice treated with
miR-493-5p agomiR before stimulation. Results: The miR-493-5p expression
in OVA-induced mice decreases significantly, accompanied by a
significant upregulation in IL-9, IRF4 and FOXO1 expression and
proportion of CD4+Th9 cells. MiR-493-5p mimic inhibits the expression of
IL-9, IRF4 and FOXO1 and Th9 cell differentiation, while the inhibitor
promotes these effects. MiR-493-5p mimic represses FOXO1 expression
through interacting with 3’UTR of FOXO1 mRNA. The rescue experiment
proves that miR-493-5p regulates the differentiation of Th9 cell and the
expression of IL-9 by targeting FOXO1. In addition, we find that
miR-493-5p agomiR treatment inhibits the FOXO1, IL-9 and IRF4
expression, decreases the proportion of CD4+ Th9 cells, alleviates the
pathological state of lung tissue and airway hyperreactivity in
OVA-induced asthma mice. Conclusions: Our study confirmed that
miR-493-5p inhibited Th9 cell differentiation in allergic asthma by
targeting FOXO1.